Is FLT4 p.Ser1275Thr (c.3824G>C) pathogenic?

FLT4 p.Ser1275Thr (c.3824G>C) is classified Uncertain significance in FLT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-13). AlphaMissense: likely benign (0.3091); Very rare (popmax 8.47e-05%, nfe).

How common is FLT4 p.Ser1275Thr (c.3824G>C) in the general population?

FLT4 p.Ser1275Thr (c.3824G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about FLT4 p.Ser1275Thr (c.3824G>C)?

AlphaMissense predicts likely benign (score 0.3091) — an in-silico prediction, not a clinical call.

FLT4 p.Ser1275Thr

c.3824G>C · rs2480811749 · VCV2443468

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3091 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3091	likely benign
REVEL	0.452	indeterminate
SaProt	LLR -8.87	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 9,843 bp · p 0.36 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,018 alleles

Overall 6.84e-05% 1/1,461,856 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: FLT4
Protein: p.Ser1275Thr
Coding: c.3824G>C
MANE Select: NM_182925
dbSNP: rs2480811749
Type: single nucleotide variant
Location: chr5:180609037 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.82 · 2 PDB
Residue 1275: a UniProt-annotated variant site (in chtd7)

Full FLT4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FLT4 p.Ser1275Asn Uncertain significance ★★ ⚠ same residue
FLT4 p.Ser1275Gly Likely pathogenic ★ ⚠ same residue
FLT4 p.Ser1275Cys Uncertain significance ★ ⚠ same residue
FLT4 p.Ser1275= Likely benign same residue
FLT4 p.Ser1275Ile Uncertain significance ★ same residue
FLT4 p.Arg1041Gln Pathogenic/Likely pathogenic ★★ same type
FLT4 p.Arg1041Trp Pathogenic/Likely pathogenic ★★ same type
FLT4 p.Arg318Ter Pathogenic/Likely pathogenic ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/flt4-p-ser1275thr (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown